Annotation Detail

Information
Associated Genes
ABL1
Associated Variants
ABL1 p.Arg351Trp (p.R351W) ( ENST00000318560.6, ENST00000372348.9 )
ABL1 p.Arg351Trp (p.R351W) ( ENST00000318560.6, ENST00000372348.9 )
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
In this in vitro study, the H1915 non-small cell lung cancer cell line (homozygous for a R351W mutation) was shown to be susceptible to dasatinib. This line showed a significant reduction in colony formation (P < 0.001) and MTT assay, which tests for NADH activity (P = 1.09 x 10^5), with dasatinib vs vehicle treatment. There was no significant difference in a lung cancer cell line without a known driver (H2126) nor in an immortalized bronchial epithelial line (Beas-2B) with either drug treatment in colony forming and MTT assays. Additionally, reduction in cell viability upon kinase inhibitor treatment could be rescued with tetracycline-induced overexpression of resistant ABL1-T315I (P < 0.001) confirming the genetic dependency of this cell line on ABL1. Moreover, a significant increased in cytotoxicity was noted with siRNA facilitated depletion of ABL1 (P < 0.005) with no significant change in H2126 or Beas-2B lines supporting ABL1 as the primary drug target.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/4787
Gene URL
https://civic.genome.wustl.edu/links/genes/4
Variant URL
https://civic.genome.wustl.edu/links/variants/1656
Rating
4
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Dasatinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
26758680
Drugs
Drug NameSensitivitySupported
DasatinibSensitivitytrue